Biomedical subjects
Publications and source records attributed to T Horsburgh.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Eight patients received either recombinant Interleukin-2 (rIL-2) alone or rIL-2 plus 5-Fluorouracil (5-FU) by constant infusion after undergoing potentially curative surgery for gastric cancer. rIL-2, given at a dose of 18 x 10(6) IU/m2/24 hours, was safely tolerated and only two episodes of WHO grade 3 toxicities occurred, both of which promptly responded to treatment and temporary interruptions of rIL-2 infusions. 5-FU infusions given at 12.5 mg/kg/24 hours did not alter the rebound lymphocytosis seen after completion of rIL-2 infusions. We conclude that the administration of rIL-2 and rIL-2 plus 5-FU to cancer patients recovering from major surgery is safe and well tolerated.
Eight patients with metastatic hypernephroma were treated with constant infusion recombinant Interleukin-2 (rIL-2), changes in renal and hepatic function and protein levels were monitored during 2 cycles of treatment. The rIL-2 infusion caused a reversible fall in ures and a non-reversible rise in creatinine. Liver function tests (bilirubin, ALT, ALP and GGT) rose during rIL-2 treatment and had returned to pretreatment levels 3 weeks after the last day of rIL-2. There was also a reversible fall in serum protein levels during rIL-2 infusion. Although constant infusion rIL-2 ameliorated much of the severe toxicities usually seen with high-dose bolus rIL-2, the non-reversible rise in serum creatinine levels is not a previously reported feature of rIL-2 therapy.
Anti-CD3 monoclonal antibody was found to enhance non-MHC restricted cellular cytotoxicity in vitro in the peripheral blood mononuclear cells from normal healthy individuals. This effect was dose dependent (maximal at 0.11 micrograms/ml) and was complete within 30 minutes. Peripheral blood mononuclear cells from 4 out of 8 cancer patients treated with Interleukin-2 were deficient in their ability to respond to anti-CD3 in vitro. In contrast, peripheral blood mononuclear cells from cancer patients who subsequently displayed a tumour response to Interleukin-2, were able to respond to anti-CD3 by enhanced non-MHC restricted cellular cytotoxicity. This study demonstrates the importance of CD3+ lymphocytes in the generation of antitumour activity following in vivo Interleukin-2 administration and the ability of CD3+ve lymphocytes to respond to anti-CD3 in vitro may indicate those patients who would benefit from Interleukin-2 therapy.